The purpose of this project is to conduct and coordinate interdisciplinary studies on cancer-prone families in order to clarify the role of genetic mechanisms and host-environmental interactions in carcinogenesis. Clinical studies of high-risk families have suggested etiologic relationships between cancers, constellations of which may cluster in individuals (multiple primary neoplasms) or may be scattered over the family tree (familial neoplastic syndromes). Discovery of laboratory test abnormalities in certain cancer-prone families, such as subclinical immune dysfunction in family members predisposed to lymphoma, melanoma, and some gastrointestinal malignancies, immunogenetic determinants in acute leukemia, Hodgkin's disease, and Waldenstrom's macroglobulinemia, DNA repair defects in leukemia and other familial neoplasm syndromes, metabolic defects in bladder cancer-prone families, and clinically apparent premalignant conditions in individuals prone to colon cancer and melanoma, have provided insights into the mechanisms of susceptibility to cancer.